Sodium Iodide → benzhydryl (5R,6R,7R)-7-[[(2Z)-2-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-3-(iodomethyl)-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 525920Notes

Reaction equation

HRID 525920 reaction equation
[C:1]([O:5][C:6](=[O:58])[C:7]([O:10]/[N:11]=[C:12](/[C:44]1[N:45]=[C:46]([NH:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[S:47][C:48]=1[Cl:49])\[C:13]([NH:15][C@@H:16]1[C:23](=[O:24])[N:22]2[C@@H:17]1[S@:18](=[O:43])[CH2:19][C:20]([CH2:41]Cl)=[C:21]2[C:25]([O:27][CH:28]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])=[O:14])([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[I-:59].[Na+]>CC(C)=O>[C:1]([O:5][C:6](=[O:58])[C:7]([O:10]/[N:11]=[C:12](/[C:44]1[N:45]=[C:46]([NH:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[S:47][C:48]=1[Cl:49])\[C:13]([NH:15][C@@H:16]1[C:23](=[O:24])[N:22]2[C@@H:17]1[S@:18](=[O:43])[CH2:19][C:20]([CH2:41][I:59])=[C:21]2[C:25]([O:27][CH:28]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])=[O:14])([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 90373324benzhydryl (5R,6R,7R)-3-(chloromethyl)-7-[[(2Z)-2-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 89488649benzhydryl (5R,6R,7R)-7-[[(2Z)-2-[5-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-3-(iodomethyl)-5,8-dioxo-5lambda4-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 67.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of (5R,6R,7R)-benzhydryl 7-((Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)acetamido)-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 5-oxide (10.5 g, 11.50 mmol) in acetone (120 mL) was added sodium iodide (2.58 g, 17.24 mmol). The mixture was stirred at room temperature over 1.5 h. LCMS indicated completion of the reaction. The solid was filtered off, the filtrate was concentrated under vacuum, the residue was purified twice by CombiFlash Rf automated silica gel chromatography (120 g column), eluting with EtOAc/Hexanes (0-45%) to afford (5R,6R,7R)-benzhydryl 7-((Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)-5-chlorothiazol-4-yl)acetamido)-3-(iodomethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 5-oxide (7.5 g, 7.75 mmol, 67.4% yield) as a light brown foaming solid. LCMS: (M+H)+: 967.9.

Workup

  1. customcompletion of the reaction
  2. filtrationThe solid was filtered off
  3. concentrationthe filtrate was concentrated under vacuum
  4. customthe residue was purified twice by CombiFlash Rf automated silica gel chromatography (120 g column)
  5. washeluting with EtOAc/Hexanes (0-45%)

Sources & evidence

ORD record
ord-ba112a7a3ff54332bd84caeddeddee8b
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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